IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis
IL-12-family cytokines play a pivotal role in neuroinflammation and neurodegeneration in relapsing–remitting multiple sclerosis (RRMS). The aim of the study was to evaluate whether two polymorphisms in IL12B gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effec...
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description | IL-12-family cytokines play a pivotal role in neuroinflammation and neurodegeneration in relapsing–remitting multiple sclerosis (RRMS). The aim of the study was to evaluate whether two polymorphisms in
IL12B
gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effect on serum level of IL-12p40 and IL-23 and degree of disability in RRMS cases. In total 156 Bulgarian patients with Expanded Disability Status Scale score ranging from 1.0 to 3.5 in remission of the disease and 379 controls were genotyped by polymerase chain reaction-based methods. The IL-12p40 and IL-23 serum levels were determined by enzyme-linked immunosorbent assay. We have found substantially higher IL-12p40 and IL-23 serum levels in cases than in controls (
p
|
doi_str_mv | 10.1007/s13760-018-01066-3 |
format | Article |
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IL12B
gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effect on serum level of IL-12p40 and IL-23 and degree of disability in RRMS cases. In total 156 Bulgarian patients with Expanded Disability Status Scale score ranging from 1.0 to 3.5 in remission of the disease and 379 controls were genotyped by polymerase chain reaction-based methods. The IL-12p40 and IL-23 serum levels were determined by enzyme-linked immunosorbent assay. We have found substantially higher IL-12p40 and IL-23 serum levels in cases than in controls (
p
< 0.01) in a sex-dependent manner. Women with RRMS had significantly higher IL-12р40 and IL-23 than men. Gender-stratified association analyses showed a significant impact of rs3212227 polymorphism on RRMS susceptibility in men. The carriers of rs3212227*CC-genotype (OR 3.390, 95% CI 1.007–11.545,
p
= 0.023) and haplotype rs17860508*2-allele/rs3212227*C-allele (OR 3.740; 95% CI 1.36–10.32,
p
= 0.007), showed higher risk of RRMS in men, in contrast to women. In women, both
IL12B
polymorphisms influencing the course, rather than genetic predisposition of RRMS. The rs17860508*22-genotype was associated with significantly lower disability (OR 0.208; 95% CI 0.055–0.725;
p
c
= 0.01) and lower IL-23 serum levels (
p
= 0.0345), while rs3212227*AA-genotype was associated with early onset of the disease (OR 2.368; 95% CI 1.007–5.608;
p
= 0.03). Our results suggest that sex-specific effects of
IL12B
polymorphisms, rs17860508 and rs3212227, on genetic predisposition and disease course of RRMS, is probably mediated by their gender-dependent functional effect on IL-12p40-containing cytokines.</description><identifier>ISSN: 0300-9009</identifier><identifier>EISSN: 2240-2993</identifier><identifier>DOI: 10.1007/s13760-018-01066-3</identifier><identifier>PMID: 30554348</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Medicine/Public Health ; Neurology ; Neuroradiology ; Neurosciences ; Original Article</subject><ispartof>Acta neurologica Belgica, 2019-03, Vol.119 (1), p.83-93</ispartof><rights>Belgian Neurological Society 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-afbd4abeeb0905a6376c004e33fbff4c32cf659793f4dd4ecba5d3f01b5ca26b3</citedby><cites>FETCH-LOGICAL-c347t-afbd4abeeb0905a6376c004e33fbff4c32cf659793f4dd4ecba5d3f01b5ca26b3</cites><orcidid>0000-0002-0028-7692</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13760-018-01066-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13760-018-01066-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30554348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miteva, Lyuba</creatorcontrib><creatorcontrib>Trenova, Anastasiya</creatorcontrib><creatorcontrib>Slavov, Georgi</creatorcontrib><creatorcontrib>Stanilova, Spaska</creatorcontrib><title>IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis</title><title>Acta neurologica Belgica</title><addtitle>Acta Neurol Belg</addtitle><addtitle>Acta Neurol Belg</addtitle><description>IL-12-family cytokines play a pivotal role in neuroinflammation and neurodegeneration in relapsing–remitting multiple sclerosis (RRMS). The aim of the study was to evaluate whether two polymorphisms in
IL12B
gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effect on serum level of IL-12p40 and IL-23 and degree of disability in RRMS cases. In total 156 Bulgarian patients with Expanded Disability Status Scale score ranging from 1.0 to 3.5 in remission of the disease and 379 controls were genotyped by polymerase chain reaction-based methods. The IL-12p40 and IL-23 serum levels were determined by enzyme-linked immunosorbent assay. We have found substantially higher IL-12p40 and IL-23 serum levels in cases than in controls (
p
< 0.01) in a sex-dependent manner. Women with RRMS had significantly higher IL-12р40 and IL-23 than men. Gender-stratified association analyses showed a significant impact of rs3212227 polymorphism on RRMS susceptibility in men. The carriers of rs3212227*CC-genotype (OR 3.390, 95% CI 1.007–11.545,
p
= 0.023) and haplotype rs17860508*2-allele/rs3212227*C-allele (OR 3.740; 95% CI 1.36–10.32,
p
= 0.007), showed higher risk of RRMS in men, in contrast to women. In women, both
IL12B
polymorphisms influencing the course, rather than genetic predisposition of RRMS. The rs17860508*22-genotype was associated with significantly lower disability (OR 0.208; 95% CI 0.055–0.725;
p
c
= 0.01) and lower IL-23 serum levels (
p
= 0.0345), while rs3212227*AA-genotype was associated with early onset of the disease (OR 2.368; 95% CI 1.007–5.608;
p
= 0.03). Our results suggest that sex-specific effects of
IL12B
polymorphisms, rs17860508 and rs3212227, on genetic predisposition and disease course of RRMS, is probably mediated by their gender-dependent functional effect on IL-12p40-containing cytokines.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Medicine/Public Health</subject><subject>Neurology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Original Article</subject><issn>0300-9009</issn><issn>2240-2993</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kMtO5DAQRS0EghbwAyxQlrMJlB9xyHIG8WippdkMWyzHKTdGeY0rQbCbf5g_5Etw08CSkqwqyfdeVR3GTjiccYDynLgsNeTAL9IDrXO5wxZCKMhFVcldtgAJkFcA1QE7JnqEVEoLXup9diChKJRUFwt2v1xx8StbY4_ZOLQv3RDHh0AdZQ_2CTPC55xGdMEHl6H36CbKQp9FbO1IoV-__vsfsQvTlOasm9spjG2yuRbjQIGO2J63LeHxRz9kd9dXfy5v89Xvm-Xlz1XupCqn3Pq6UbZGrKGCwup0mkvropS-9l45KZzXRVVW0qumUehqWzTSA68LZ4Wu5SH7sc0d4_B3RppMF8hh29oeh5mM4EWpC11xmaRiK3VpQ4rozRhDZ-OL4WA2aM0WrUlozTtaszGdfuTPdYfNl-UTZBLIrYDSV7_GaB6HOfbp5u9i3wA40YcL</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Miteva, Lyuba</creator><creator>Trenova, Anastasiya</creator><creator>Slavov, Georgi</creator><creator>Stanilova, Spaska</creator><general>Springer International Publishing</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0028-7692</orcidid></search><sort><creationdate>20190301</creationdate><title>IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis</title><author>Miteva, Lyuba ; Trenova, Anastasiya ; Slavov, Georgi ; Stanilova, Spaska</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-afbd4abeeb0905a6376c004e33fbff4c32cf659793f4dd4ecba5d3f01b5ca26b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Medicine/Public Health</topic><topic>Neurology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Original Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miteva, Lyuba</creatorcontrib><creatorcontrib>Trenova, Anastasiya</creatorcontrib><creatorcontrib>Slavov, Georgi</creatorcontrib><creatorcontrib>Stanilova, Spaska</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Acta neurologica Belgica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miteva, Lyuba</au><au>Trenova, Anastasiya</au><au>Slavov, Georgi</au><au>Stanilova, Spaska</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis</atitle><jtitle>Acta neurologica Belgica</jtitle><stitle>Acta Neurol Belg</stitle><addtitle>Acta Neurol Belg</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>119</volume><issue>1</issue><spage>83</spage><epage>93</epage><pages>83-93</pages><issn>0300-9009</issn><eissn>2240-2993</eissn><abstract>IL-12-family cytokines play a pivotal role in neuroinflammation and neurodegeneration in relapsing–remitting multiple sclerosis (RRMS). The aim of the study was to evaluate whether two polymorphisms in
IL12B
gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effect on serum level of IL-12p40 and IL-23 and degree of disability in RRMS cases. In total 156 Bulgarian patients with Expanded Disability Status Scale score ranging from 1.0 to 3.5 in remission of the disease and 379 controls were genotyped by polymerase chain reaction-based methods. The IL-12p40 and IL-23 serum levels were determined by enzyme-linked immunosorbent assay. We have found substantially higher IL-12p40 and IL-23 serum levels in cases than in controls (
p
< 0.01) in a sex-dependent manner. Women with RRMS had significantly higher IL-12р40 and IL-23 than men. Gender-stratified association analyses showed a significant impact of rs3212227 polymorphism on RRMS susceptibility in men. The carriers of rs3212227*CC-genotype (OR 3.390, 95% CI 1.007–11.545,
p
= 0.023) and haplotype rs17860508*2-allele/rs3212227*C-allele (OR 3.740; 95% CI 1.36–10.32,
p
= 0.007), showed higher risk of RRMS in men, in contrast to women. In women, both
IL12B
polymorphisms influencing the course, rather than genetic predisposition of RRMS. The rs17860508*22-genotype was associated with significantly lower disability (OR 0.208; 95% CI 0.055–0.725;
p
c
= 0.01) and lower IL-23 serum levels (
p
= 0.0345), while rs3212227*AA-genotype was associated with early onset of the disease (OR 2.368; 95% CI 1.007–5.608;
p
= 0.03). Our results suggest that sex-specific effects of
IL12B
polymorphisms, rs17860508 and rs3212227, on genetic predisposition and disease course of RRMS, is probably mediated by their gender-dependent functional effect on IL-12p40-containing cytokines.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30554348</pmid><doi>10.1007/s13760-018-01066-3</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0028-7692</orcidid></addata></record> |
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title | IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis |
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